Ozone → (4R)-4-(2-Hydroxyethyl)-4-methoxymethyl-1-[(1R)-1-phenylethyl]pyrrolidin-2-one

Participants

Reaction Steps

A solution of (4R)-4-allyl-4-methoxymethyl-1-[(1R)-1-phenylethyl]pyrrolidin-2-one (3.28 g, 12.0 mmol) in methanol (20 mL)-dichloromethane (20 mL) was bubbled with ozone gas at −70° C. and stirred at the same temperature for 30 minutes. Ozone bubbling was stopped when the reaction solution was turned dark blue, and then the reaction solution was bubbled with nitrogen gas until the solution turned colorless. Sodium borohydride (454 mg, 12.0 mmol) was added at the same temperature, and the mixture was heated to room temperature over two hours. After heating, sodium borohydride (227 mg, 6.0 mmol) was added and the mixture was stirred for 24 hours. Then, sodium borohydride (113 mg, 3.0 mmol) was further added and the mixture was stirred for 0.5 hour. A saturated ammonium chloride solution (10 mL) was added, and the mixture was stirred for 10 minutes. Then, the reaction solution was poured into a mixture of ethyl acetate (50 mL) and water (50 mL), followed by extraction with ethyl acetate (200 mL). The organic layer was washed with brine (50 mL), and then dried over anhydrous sodium sulfate and filtered. The filtrate was then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:methanol=10:0→10:1) to give 2.85 g (86%) of the title compound as a colorless viscous oil.

Provenance & Evidence